Exploration of Deficient Brain Uptake of F-18-AV-300 Rats
碩士 === 長庚大學 === 醫學影像暨放射科學系 === 101 === Introduction: [18F]AV-300 has been developed as a novel tracer for improvement of PET imaging targeting pancreatic VMAT2. Previous study demonstrated [18F]AV-300 PET failed to image rat brain in despite of the fact that [18F]AV-300 possesses high specific affin...
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ndltd-TW-101CGU057700032015-10-13T22:06:56Z http://ndltd.ncl.edu.tw/handle/18038812895736898711 Exploration of Deficient Brain Uptake of F-18-AV-300 Rats 氟-18-AV-300大鼠腦攝取不足之探討 Ting Wei E 鄂婷偉 碩士 長庚大學 醫學影像暨放射科學系 101 Introduction: [18F]AV-300 has been developed as a novel tracer for improvement of PET imaging targeting pancreatic VMAT2. Previous study demonstrated [18F]AV-300 PET failed to image rat brain in despite of the fact that [18F]AV-300 possesses high specific affinity to bind striatal VMAT2 in rat brain. The poor cerebral uptake of [18F]AV-300 might be due to: (1) limited penetration by the blood-brain-barrier (BBB), and/ or (2) pumping out by P-glycoprotein (P-gp) on BBB. To clarify the cause of the poor uptake of [18F]AV-300 in rat brain, the change of cerebral uptake of [18F]AV-300 was investigated by: (1) using focus ultrasound (FUS) to induce temporal BBB disruption, and (2) blocking efflux function of P-gp by systemic treatment with cyclosporin A (CsA). Methods: Part one: The left cerebral hemispheres of male SD rats were treated with FUS 10 min prior to intravenous [18F]AV-300 injection. The change of [18F]AV-300 uptakes in FUS-treated side was evaluated by dynamic [18F]AV-300 brain PET scan. Part two: The male SD rats in the test group were intravenously administrated with cyclosporine A (50 mg/kg) 30 min prior to [18F]AV-300 injection. The rats injected with cyclosporine A-free vehicle were served as the sham control. The brain tissue was dissected to determine the distribution of the tracer. Brain PET scan was performed for 120 min and then the brain sections were subject to autoradiography. The change of [18F]AV-300 uptakes was compared between the test group, the sham and the normal control. In addition, the striatal homogenates and the arterial blood were analyzed for metabolism. The free fraction of [18F]AV-300 in arterial blood was also determined for the test group and the normal control. Part three: One rat was treated with CsA and followed with FUS before [18F]AV-300 injection. Dynamic brain PET scan was acquired for 180 min. The change of [18F]AV-300 uptake was compared with other groups and the normal control. Results: Part one: The uptakes (%ID/ml) of [18F]AV-300 in striatum were not significantly different neither in FUS-treated (treated side: 0.10±0.01;contralateral side: 0.09±0.01) or control (0.08±0.01) rats. Part two: The uptakes of [18F]AV-300 in striatum were enhanced to 0.70±0.29 %ID/ml; meanwhile, the uptakes of [18F]AV-300 in cerebellum were also increased to 0.30 ± 0.16%ID/ml. SUVRST/CB values were increased to 2.77 ± 0.19. The results of autoradiography, ex vivo regional brain distribution and PET were consistent. Treated with CsA was not affect the metabolism of [18F]AV-300 in both arterial blood and striatum. However, the free fraction of [18F]AV-300 was increased 2.3-fold after CsA treatment. Part three: In CsA-FUS combined treated rat, the uptake of [18F]AV-300 on the treated side was not significantly different with contralateral side. Conclusion: The uptake of [18F]AV-300 was not improved in FUS-induced BBB disruption rats brain. Therefore, the poor uptake of [18F]AV-300 in rats brain is not due to the BBB restriction. Enhanced brain uptake of [18F]AV-300 in CsA-treated rats suggested that the tracer might be a substrate for P-glycoprotein. The metabolism was not change while the rats were treated with CsA. In the CsA-treated rats, the free fraction of [18F]AV-300 was increased to enhance the uptake of [18F]AV-300 in rats brain. In the future, the mechanism of [18F]AV-300 increased uptake in rats which treated CsA should be explored. S. P. Wey 魏孝萍 2013 學位論文 ; thesis 97 |
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碩士 === 長庚大學 === 醫學影像暨放射科學系 === 101 === Introduction: [18F]AV-300 has been developed as a novel tracer for improvement of PET imaging targeting pancreatic VMAT2. Previous study demonstrated [18F]AV-300 PET failed to image rat brain in despite of the fact that [18F]AV-300 possesses high specific affinity to bind striatal VMAT2 in rat brain. The poor cerebral uptake of [18F]AV-300 might be due to: (1) limited penetration by the blood-brain-barrier (BBB), and/ or (2) pumping out by P-glycoprotein (P-gp) on BBB. To clarify the cause of the poor uptake of [18F]AV-300 in rat brain, the change of cerebral uptake of [18F]AV-300 was investigated by: (1) using focus ultrasound (FUS) to induce temporal BBB disruption, and (2) blocking efflux function of P-gp by systemic treatment with cyclosporin A (CsA).
Methods: Part one: The left cerebral hemispheres of male SD rats were treated with FUS 10 min prior to intravenous [18F]AV-300 injection. The change of [18F]AV-300 uptakes in FUS-treated side was evaluated by dynamic [18F]AV-300 brain PET scan.
Part two: The male SD rats in the test group were intravenously administrated with cyclosporine A (50 mg/kg) 30 min prior to [18F]AV-300 injection. The rats injected with cyclosporine A-free vehicle were served as the sham control. The brain tissue was dissected to determine the distribution of the tracer. Brain PET scan was performed for 120 min and then the brain sections were subject to autoradiography. The change of [18F]AV-300 uptakes was compared between the test group, the sham and the normal control. In addition, the striatal homogenates and the arterial blood were analyzed for metabolism. The free fraction of [18F]AV-300 in arterial blood was also determined for the test group and the normal control.
Part three: One rat was treated with CsA and followed with FUS before [18F]AV-300 injection. Dynamic brain PET scan was acquired for 180 min. The change of [18F]AV-300 uptake was compared with other groups and the normal control.
Results: Part one: The uptakes (%ID/ml) of [18F]AV-300 in striatum were not significantly different neither in FUS-treated (treated side: 0.10±0.01;contralateral side: 0.09±0.01) or control (0.08±0.01) rats.
Part two: The uptakes of [18F]AV-300 in striatum were enhanced to 0.70±0.29 %ID/ml; meanwhile, the uptakes of [18F]AV-300 in cerebellum were also increased to 0.30 ± 0.16%ID/ml. SUVRST/CB values were increased to 2.77 ± 0.19. The results of autoradiography, ex vivo regional brain distribution and PET were consistent. Treated with CsA was not affect the metabolism of [18F]AV-300 in both arterial blood and striatum. However, the free fraction of [18F]AV-300 was increased 2.3-fold after CsA treatment.
Part three: In CsA-FUS combined treated rat, the uptake of [18F]AV-300 on the treated side was not significantly different with contralateral side.
Conclusion: The uptake of [18F]AV-300 was not improved in FUS-induced BBB disruption rats brain. Therefore, the poor uptake of [18F]AV-300 in rats brain is not due to the BBB restriction. Enhanced brain uptake of [18F]AV-300 in CsA-treated rats suggested that the tracer might be a substrate for P-glycoprotein. The metabolism was not change while the rats were treated with CsA. In the CsA-treated rats, the free fraction of [18F]AV-300 was increased to enhance the uptake of [18F]AV-300 in rats brain. In the future, the mechanism of [18F]AV-300 increased uptake in rats which treated CsA should be explored.
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author2 |
S. P. Wey |
author_facet |
S. P. Wey Ting Wei E 鄂婷偉 |
author |
Ting Wei E 鄂婷偉 |
spellingShingle |
Ting Wei E 鄂婷偉 Exploration of Deficient Brain Uptake of F-18-AV-300 Rats |
author_sort |
Ting Wei E |
title |
Exploration of Deficient Brain Uptake of F-18-AV-300 Rats |
title_short |
Exploration of Deficient Brain Uptake of F-18-AV-300 Rats |
title_full |
Exploration of Deficient Brain Uptake of F-18-AV-300 Rats |
title_fullStr |
Exploration of Deficient Brain Uptake of F-18-AV-300 Rats |
title_full_unstemmed |
Exploration of Deficient Brain Uptake of F-18-AV-300 Rats |
title_sort |
exploration of deficient brain uptake of f-18-av-300 rats |
publishDate |
2013 |
url |
http://ndltd.ncl.edu.tw/handle/18038812895736898711 |
work_keys_str_mv |
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